Incidence of serious infections in the working-age Japanese adult population with rheumatoid arthritis treated with tumor necrosis factor-α inhibitors and interleukin-6 inhibitors: A nationwide retrospective cohort study

Aim: This retrospective cohort study aimed to compare the risk of serious infections in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α inhibitors (TNFαi) and interleukin-6 inhibitors (IL-6i), with no prior use of biological disease-modifying antirheumatic drugs (bDMARDs).

Methods: We employed the nationwide insurance claims database encompassing the years 2005 to 2018 in Japan. The inclusion criteria specified patients who were prescribed any type of bDMARDs, including TNFαi and IL-6i. The following exclusion criteria were applied: missing prescription dates, RA not diagnosed, below 16 years of age, bDMARDs prescribed within 6 months of registration, RA diagnosed post-bDMARDs prescription, and incidence of serious infections within 2 weeks before bDMARDs therapy. We applied stabilized inverse probability weights and utilized a Cox regression model to estimate the risk of serious infections associated with TNFαi and IL-6i.

Results: The cohort of 2493 patients with RA was categorized into a TNFαi group and an IL-6i group of 2018 and 475 participants, respectively. The median follow-up duration (interquartile range) was 347 (147-820) days in the TNFαi group and 369 (149-838) days in the IL-6i group. In the inverse probability-weighted cohort, the incidence rates (95% confidence interval) of serious infections were 2.13 (1.65-2.71) and 3.25 (2.15-4.69) per 100 person-years for the TNFαi and IL-6i groups, respectively. The hazard ratio (95% confidence interval) comparing the TNFαi group to the IL-6i group was 0.66 (0.36-1.20, p = 0.168).

Discussion: The results underscore the lack of evidence to preferentially favor either TNFαi or IL-6i as later-line therapy in the management of bDMARDs-naive RA to mitigate the risk of serious infections.